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Combined nephrotoxic effects of fluoride, water hardness, and microcystin-LR associated with CKDu in Sri Lanka: a zebrafish (Danio rerio) model approach.
| Environmental Geochemistry and Health | Imanthi KPA, Wanigasuriya JKP, Perera PPR, Jayasundara N, Manage PM. | 48(8):354.
CKDu Sri Lanka Zebrafish Kidney Nephrotoxicity Animal Study

Abstract

Original abstract online at
https://link.springer.com/article/10.1007/s10653-026-03226-4

Chronic Kidney Disease of unknown etiology (CKDu) is a major public health concern in several agricultural regions of Sri Lanka. In areas with a high prevalence of CKDu, elevated concentrations of fluoride and water hardness have been consistently reported in domestic wells, along with emerging evidence of cyanotoxin contamination. This study investigated the potential renal toxicity associated with environmentally relevant concentrations of fluoride, water hardness, and microcystin-LR (MC-LR) using a zebrafish (Danio rerio) model. Twenty groundwater samples were collected from the CKDu-endemic Padaviya region in the North Central Province. Mean fluoride and total hardness concentrations were 1.12±0.64 mg L–1 and 424.2±126.1 mg L-1, respectively, while MC-LR was detected in 45% of the samples (mean: 0.96 µg L–1). Zebrafish embryos (2 h post fertilisation) were exposed to the concentrations reflecting maximum and minimum field observation values. Single exposures to fluoride, hardness, and MC-LR resulted in moderate mortality and developmental abnormalities, whereas combined exposure produced significantly higher mortality, 50.0±1.15% (p<0.05), and increased incidence of oedema, spinal curvature, and growth retardation in larvae. Histopathological examinations of larvae exposed to the combined treatment revealed noticeable pronephric alterations, including tubular vacuolation, cellular swelling, and inflammation indicative of renal damage. Chronic exposure to zebrafish resulted in significant upregulation in Kidney Injury Molecule (KIM-1) gene expression, representing renal tubular injury. These findings suggest that the combined chronic exposure to multiple well water contaminants may induce nephrotoxic effects at concentrations relevant to CKDu-endemic surroundings. Although the results do not establish direct causation, they highlight the importance of considering mixture toxicity in environmental risk assessment and drinking-water management in CKDu-affected regions to address the health issue.

Data availability

No datasets were generated or analysed during the current study.

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Acknowledgements

‘Centre for Water Quality and Algae Research, Faculty of Applied Sciences, University of Sri Jayewardenepura, Sri Lanka’, ‘Centre for Kidney Research, Faculty of Medical Sciences, University of Sri Jayewardenepura, Sri Lanka’, Department of Pathology, Faculty of Medical Sciences, University of Sri Jayewardenepura, Sri Lanka’ and ‘Animal house, Faculty of Medical Sciences, University of Sri Jayewardenepura, Sri Lanka’ are acknowledged for the support.

Funding

University Grant (University of Sri Jayewardenepura, Sri Lanka)–ASP/01/RE/SCI/2022/16.

Author information

Authors and Affiliations

  1. Centre for Water Quality and Algae Research, Faculty of Applied Sciences, University of Sri Jayewardenepura, Nugegoda, Sri Lanka

    K. P. A. Imanthi & P. M. Manage

  2. Faculty of Graduate Studies, University of Sri Jayewardenepura, Nugegoda, Sri Lanka

    K. P. A. Imanthi & P. P. R. Perera

  3. Department of Medicine, Faculty of Medical Sciences, University of Sri Jayewardenepura, Nugegoda, Sri Lanka

    J. K. P. Wanigasuriya

  4. Centre for Kidney Research, Faculty of Medical Sciences, University of Sri Jayewardenepura, Nugegoda, Sri Lanka

    P. P. R. Perera

  5. Department of Biochemistry, Faculty of Medical Sciences, University of Sri Jayewardenepura, Nugegoda, Sri Lanka

    P. P. R. Perera

  6. Nicholas School of the Environment, Duke University, Durham, North Carolina, USA

    Nishad Jayasundara

Contributions

Conceptualisation: P.M. Manage, J.K.P. Wanigasuriya, Nishad Jayasundara Investigation and Data Collection: K.P.A. Imanthi, P.M. Manage Resources: K.P.A. Imanthi, P.M. Manage, J.K.P. Wanigasuriya, P.P.R. Perera, Nishad Jayasundara Writing and reviewing—Original Draft: K.P.A. Imanthi, Review: K.P.A. Imanthi, P.M. Manage, J.K.P. Wanigasuriya, P.P.R. Perera, Nishad Jayasundara All authors have read and agreed to publish the final version of the manuscript.

Corresponding author

Correspondence to P. M. Manage.

Ethics declarations

Conflict of interest

The authors have no relevant financial or non-financial interests to disclose.

Ethical approval

Ethical clearance was obtained from the Ethics Review Committee- Animal Studies, Faculty of Graduate Studies, University of Sri Jayewardenepura, Sri Lanka (FGS/ERCAS/2022/02/01).

Clinical trial number

Not applicable.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 234 KB) (download DOCX )